This proposal has, as its objective, the elucidation of 3 areas of human biology relevant to vascular injury in immunologic diseases. The first project brings together a broadly interdisciplinary team of investigators in a study of the pathophysiology of Raynaud's syndrome. This study will examine the pathophysiologic responses of patients (and controls) to cold challenge delivered by local cold immersion of a limb, inhalation of cold air, and generalized body cooling in an environmental chamber. Both peripheral vascular and pulmonary responses will be monitored. This project will also expand preliminary studies on in vivo catecholamine metabolism in Raynaud's syndrome, with particular emphasis on norepinephrine release and turnover. Finally, the above parameters will be correlated with in vitro measurement of alpha and beta adrenergic receptor status and functional activity as represented by the patients' peripheral blood lymphocytes and platelets. The second research project will continue a detailed examination of the molecular basis of self-association of monoclonal IgG cryoglobulins from patients with essential cryoglobulinemia. Both physicochemical and primary structural analyses are planned. The third project closely examines the responses of human platelets (secretion and aggregation) to immunologic reactants, specifically IgG and complement components bound to a particulate surface. The yeast carbohydrate, zymosan, is employed as a model probe. Major emphasis is given to extending preliminary evidence for complement-mediated potential of platelet responses that is apparently dependent on particle-bound C5, C6 and C7. Biochemical characterization of platelet Fc (IgG)-receptors and (putative) complement receptors are longer-range goals of this project.